Radiation Therapy Significantly Contributes To Loss Of Cardiac Function After Treatment For Breast Cancer

Radiotherapy (RT) increases the risk of acute coronary events (ACE) in breast cancer (BC) patients with a relative increase of ∼16% per Gy mean heart dose (MHD) in the first 9 years after treatment. The association between thoracic RT and myocardial dysfunction is less clear. Insight into the functional effects of RT dose on the heart and its substructures will offer new opportunities for optimizing RT treatment plans by decreasing the dose to relevant critical cardiac substructures. The main aim of this study was to test the hypothesis that cardiac irradiation is associated with changes in systolic and diastolic cardiac function in BC patients. In this cross-sectional study, systolic and diastolic function was assessed by echocardiography in 109 female BC patients treated with postoperative RT between 2005 and 2011. For each patient, the individual dose-volume histogram (DVH) parameters of the whole heart and its substructures, including the coronary arteries, were collected from planning-CT scans. The primary endpoint was systolic and diastolic function, assessed by echocardiography. As a measure of systolic function, left ventricle ejection fraction (LVEF) was assessed. To detect subclinical changes in systolic function, the global longitudinal strain (GLS) of the left ventricle (LV) was determined. As a measure of diastolic function the mean of e’septal and e’lateral was used. To test the relationship between cardiac dysfunction and radiation dose to the heart and its substructures stepwise multivariable linear regression analysis was used. The median time between BC diagnosis and echocardiography was 7 years (range 4-10). No associations between DVH parameters and LVEF was found. In a multivariable analysis, the GLS of the LV was associated with the MHD (median: 2.24 Gy, range: 0.61-11.34), V5 of the left ventricle (median: 1.74%, range: 0.00-87.10) and the maximum dose to the left main coronary artery (Dmax LMCA) (median: 1.78 Gy, range: 0.45-7.42). The most significant association was found with the Dmax LMCA (p=0.013). Decreased diastolic function was associated with higher maximum dose to the ascending aorta (p=0.003) (median: 3.18 Gy, range: 1.04-11.50) and with higher age (p<0.001) and the presence of hypertension at baseline (p=0.009). Thus, both systolic and diastolic function were associated with individual radiation dose to cardiac structures. This is the first study showing a significant relationship between RT for BC and early subclinical cardiac systolic and diastolic dysfunction. Effects of RT are already observed within 7 years of RT and after relatively low incidental cardiac dose levels. This study confirms the importance of reducing radiation dose to the heart and its substructures to limit the risk of cardiac dysfunction.